Comparisons of treatment outcomes of epcoritamab versus chemoimmunotherapy, polatuzumab-based regimens, tafasitamab-based regimens, or chimeric antigen receptor T-cell therapy, in third-line or later relapsed/refractory large B-cell lymphoma.

Many therapies are available for the treatment of relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) after ≥ 2 lines of therapy, albeit with scant evidence on the comparative effectiveness of these therapies. This study used inverse probability of treatment weighting to indirectly compare treatment outcomes of epcoritamab from the EPCORE NHL-1 trial with individual patient data from clinical practice cohorts treated with chemoimmunotherapy (CIT) and novel therapies (polatuzumab-based regimens, tafasitamab-based regimens, and chimeric antigen receptor T-cell [CAR T] therapies) for third-line or later R/R large B-cell lymphoma (LBCL) and DLBCL. In this analysis, epcoritamab demonstrated significantly better response rates and overall survival rates than CIT, polatuzumab-based regimens, and tafasitamab-based regimens. No statistically significant differences in response rates or survival were found for epcoritamab compared with CAR T in R/R LBCL.

Effect of orientation angle for needle-free jet injection.

In this paper, we report on the delivery efficiency of needle-free jet injections using injectors with typical jet speed vj≈140m/s, orifice diameter do=157µm, and volume V=0.1 mL. The target substrates were either hydrogel tissue phantoms or porcine tissues combined with excised human skin. The novelty of this study is two-fold: First, we investigate the influence of injection angle relative to the skin surface, and second, we also study the influence of the jet path relative to the orientation of muscle fibers. While most commercial jet injectors employ a fitting that would render the device normal to the skin surface, recent studies have proposed oblique injections, which may be beneficial for intradermal or subcutaneous tissue injection. Furthermore, for deeper intramuscular injections, we propose that an angled jet path taking the muscle fiber orientation into account may result in a bolus or dispersion zone that is conducive to increased cellular uptake of the drug.

Epcoritamab monotherapy in patients with relapsed or refractory follicular lymphoma (EPCORE NHL-1): a phase 2 cohort of a single-arm, multicentre study.

BACKGROUND: A standard of care and optimal duration of therapy have not been established for patients with multiply relapsed or refractory follicular lymphoma. The aim of this study was to evaluate epcoritamab, a novel CD3 × CD20 bispecific antibody, in the third-line and later setting of follicular lymphoma. METHODS: EPCORE NHL-1 is a multicohort, single-arm, phase 1-2 trial conducted at 88 sites across 15 countries. Here, we report the primary analysis of patients with relapsed or refractory follicular lymphoma in the phase 2 part of the trial, which included the pivotal (dose expansion) cohort and the cycle 1 optimisation cohort. Eligible patients were aged 18 years or older, had relapsed or refractory CD20+ follicular lymphoma (grade 1-3A), an Eastern Cooperative Oncology Group performance status of up to 2, and had received at least two previous lines of therapy (including an anti-CD20 monoclonal antibody and an alkylating agent or lenalidomide). Patients were treated with subcutaneous epcoritamab 48 mg in 28-day cycles: weekly in cycles 1-3, biweekly in cycles 4-9, and every 4 weeks until disease progression or unacceptable toxicity. To mitigate the risk and severity of cytokine release syndrome, in the pivotal cohort, cycle 1 consisted of a step-up dosing regimen of a 0·16-mg priming dose on day 1 and a 0·80-mg intermediate dose on day 8, followed by subsequent 48-mg full doses and prophylactic prednisolone 100 mg; in the cycle 1 optimisation cohort, a second intermediate dose of 3 mg on day 15, adequate hydration, and prophylactic dexamethasone 15 mg were evaluated during cycle 1 to further reduce risk and severity of cytokine release syndrome. Primary endpoints were independently reviewed overall response rate for the pivotal cohort and the proportion of patients with grade 2 or worse and any-grade cytokine release syndrome for the cycle 1 optimisation cohort. Analyses were done in all enrolled patients who had received at least one dose of epcoritamab. This study is registered with ClinicalTrials.gov, NCT03625037, and is ongoing. FINDINGS: Between June 19, 2020, and April 21, 2023, 128 patients (median age 65 years [IQR 55-72]; 49 [38%] female and 79 [62%] male) were enrolled and treated in the pivotal cohort (median follow-up 17·4 months [IQR 9·1-20·9]). The overall response rate was 82·0% (105 of 128 patients; 95% CI 74·3-88·3), with a complete response rate of 62·5% (80 of 128; 95% CI 53·5-70·9). The most common grade 3-4 treatment-emergent adverse event was neutropenia in 32 (25%) of 128 patients. Grade 1-2 cytokine release syndrome was reported in 83 (65%) of 128 patients; grade 3 cytokine release syndrome was reported in two (2%). Immune effector cell-associated neurotoxicity syndrome was reported in eight (6%) of 128 patients (five [4%] grade 1; three [2%] grade 2). Between Oct 25, 2022, and Jan 8, 2024, 86 patients (median age 64 years [55-71]; 37 [43%] female and 49 [57%] male) were enrolled and treated in the cycle 1 optimisation cohort. The incidence of cytokine release syndrome was 49% (42 of 86 patients; eight [9%] grade 2; none of grade 3 or worse), with no reported immune effector cell-associated neurotoxicity syndrome. INTERPRETATION: Epcoritamab monotherapy showed clinically meaningful activity in patients with multiply relapsed or refractory follicular lymphoma, and had a manageable safety profile. FUNDING: Genmab and AbbVie.

Treatment Outcomes with Standard of Care in Relapsed/Refractory Diffuse Large B-Cell Lymphoma: Real-World Data Analysis.

INTRODUCTION: Despite new therapies for relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL), treatments with chemotherapy, single-agent rituximab/obinutuzumab, single-agent lenalidomide, or combinations of these agents continue to be commonly used. METHODS: This retrospective study utilized longitudinal data from 4226 real-world electronic health records to characterize outcomes in patients with R/R DLBCL. Eligible patients were diagnosed with DLBCL between January 2010 and March 2022 and had R/R disease treated with ≥ 1 prior systemic line of therapy (LOT), including ≥ 1 anti-CD20-containing regimen. RESULTS: A total of 573 patients treated with ≥ 1 prior LOT were included (31.2% and 13.4% with ≥ 2 and ≥ 3 prior LOTs, respectively). Median duration of follow-up was 7.7 months. Most patients (57.1%) were male; mean standard deviation (SD) age was 63 (14.7) years. Overall and complete response rates (95% confidence interval (CI) were 52% (48-56) and 23% (19-27). Median duration of response and duration of complete response were 3.5 and 18.4 months. Median progression-free and overall survival (95% CI) was 3.0 (2.8-3.3) and 12.9 (10.1-16.9) months, respectively. Patients with a higher number of prior LOTs, primary refractoriness, refractoriness to last LOT, refractoriness to last anti-CD20-containing regimen, and prior CAR T exposure had worse outcomes (i.e., challenging-to-treat R/R DLBCL) compared with those without these characteristics. CONCLUSIONS: Outcomes in patients with R/R DLBCL treated with chemotherapy, single-agent rituximab/obinutuzumab, single-agent lenalidomide, or combinations of these agents remain poor, especially for those with challenging-to-treat R/R DLBCL. These findings underscore the unmet need for new, safe, and effective therapies, especially for challenging-to-treat R/R DLBCL populations.

The House Cup: Using Longitudinal Gamification to Improve Didactic Attendance.

OBJECTIVE: Determine if a point-based attendance system combined with longitudinal gamification is feasible and improves didactic session attendance and learner perceptions at our internal medicine residency. METHODS: A prospective before-after cohort study. Weekly attendance was tracked from June 2022 through April 2023 at our university-affiliated internal medicine residency program. We implemented a point-based longitudinal game incentivizing residents to attend didactics with positive reinforcement in July 2022 (C: carrot). We added tiered positive reinforcement and positive punishment to the game in January 2023 (CS: carrot and stick). Attendance during these periods was compared to pre (P) and postintervention (S). Perceptions were assessed during the P, C, and CS periods with Likert scale ratings. RESULTS: CS was associated with higher attendance than other study periods (P = .002). Median attendance was P-51% (IQR 37.5-64.5), C-65% (IQR 50-74), CS-81% (IQR 78-94), and S-66% (IQR 63-71). Perceptions were similar during pre and intervention study periods, including perceptions of camaraderie (P-4.4, C-4.4, CS-4.5; P = .56), interest in attending didactic sessions (P-3.7, C-3.4, CS-3.2; P = .21), and mandate as the primary reason for attending didactics (P-3.1, C-3.1, CS-3.2; P = .96). CONCLUSIONS: A point-based attendance system combined with a longitudinal game that included tiered positive reinforcement and positive punishment was feasible and associated with higher didactic attendance but not associated with changes in resident perceptions.

A retrospective analysis of neurogenic orthostatic hypotension in long-term care facility residents with recurrent falls.

INTRODUCTION: Approximately 50 % of residents in long-term care facilities fall yearly and orthostatic hypotension accounts for a significant portion of them. Neurogenic orthostatic hypotension - a subtype of orthostatic hypotension - is important to be recognized as its management is far more complex; undertreatment of these older adults can lead to recurrent falls, high healthcare cost burden, and increased morbidity and mortality. The primary purpose of our study was to describe the rate of neurogenic orthostatic hypotension in older adults in a long-term care facility, with a secondary purpose to describe risk factors for neurogenic orthostatic hypotension in this population. METHODS: We conducted a retrospective case-control study of residents with recurrent falls at the Dayton Veteran's Affairs long-term care facility. Charts were manually reviewed. Inclusion criterion was three or more falls and age 65 or greater; we did not have exclusion criteria. ICD10 codes and most recent primary care physician notes were used to identify comorbidity diagnoses. Recent orthostatic vitals were used to assess orthostatic hypotension or neurogenic orthostatic hypotension diagnoses. RESULTS: Of our sample of 224 residents, we observed a prevalence of 20.5 % for neurogenic orthostatic hypotension and 32.1 % for orthostatic hypotension. Neither of them had diagnosis of neurogenic orthostatic hypotension documented. Parkinson's disease was associated with neurogenic orthostatic hypotension (OR-4.3; p = 0.002). Hypertension was prevalent in 69.6 % of residents with orthostatic vitals suggestive of neurogenic orthostatic hypotension. CONCLUSION: Older adults with recurrent falls at a long-term care facility meet criteria for neurogenic orthostatic hypotension diagnosis far more often than is documented. Common comorbidities associated with neurogenic orthostatic hypotension in this population include Parkinson's disease.

Confidence and Utilization are Poorly Associated with Point-of-Care Ultrasound Competency among Internal Medicine Trainees.

INTRODUCTION: Point-of-Care Ultrasound (POCUS) is the utilization of bedside ultrasound by clinicians. Its portable and rapid diagnostic capabilities make it an excellent tool for deployment and mobile military settings. However, formal and uniform POCUS training is lacking. Furthermore, the evaluation of these curricula often relies on confidence assessment. Our objective was to assess the relationships between confidence, frequency of utilization, and image interpretation knowledge among our Internal Medicine residents before and after the implementation of a formal curriculum. MATERIALS AND METHODS: In November 2020, we implemented a longitudinal, flipped-classroom, academic half-day curriculum, conducting a prospective before-after cohort evaluation of its implementation. The POCUS curriculum was implemented as a longitudinal, asynchronous, flipped-classroom activity with workshop sessions during one academic half-day per month. We measured confidence via a Likert scale and utilization frequency via a five-point scale. Six multiple-choice questions (MCQ) with ultrasound videos assessed image interpretation competency. The image interpretation score was reported as percent correct. We related confidence and utilization to the image interpretation score. RESULTS: Ninety-nine residents were eligible for participation. Fifty-four (55%) completed a pre-curriculum assessment and 45 (45%) completed a post-curriculum assessment. Average image interpretation scores were 41% pre-curriculum and 51% post-curriculum (P =0.02). Pre-curriculum residents were on average unconfident (mean=2.56), and post-curriculum residents were on average confident (mean=3.62). Pre-curriculum residents used POCUS occasionally (mean=2.02, count 13 (24%) never utilizing). Post-curriculum residents used POCUS occasionally (mean=2.42, count 4 (9%) never utilizing). Pre- and post-curriculum confidence were not significantly associated with image interpretation scores (pre-curriculum: r=-0.10, P =0.50; post-curriculum: r=0.24, P =0.11). Pre- and post-curriculum utilization were not significantly associated with image interpretation scores (pre-curriculum: r=0.15, P =0.28; post-curriculum: r=0.02, P =0.90). The number of curriculum sessions attended was significantly associated with higher image interpretation scores (r=0.30, P =0.003). CONCLUSIONS: Our study suggests that POCUS confidence and informal utilization do not correlate with image interpretation knowledge on MCQs among Internal Medicine residents. These findings support assessing direct measures of knowledge, rather than confidence, as an endpoint in evaluating POCUS curricula among Internal Medicine residents.

Implementation and Evaluation of a Longitudinal Flipped-Classroom Point-of-Care Ultrasound Curriculum at an Internal Medicine Residency Program.

BACKGROUND: Point-of-care ultrasound (POCUS) has extensive clinical utility in internal medicine, but formal and uniform curricula in internal medicine are lacking. OBJECTIVE: To determine the effectiveness of a longitudinal, flipped-classroom, academic half-day curriculum on internal medicine resident confidence, utilization, and changes in clinical management. METHODS: We implemented an asynchronous, flipped-classroom, academic half-day curriculum from November 2020 to November 2021 and conducted an evaluation with a prospective, before-after cohort study. Curriculum included 4 rotating sessions comprised of 20 to 30 min of image interpretation followed by 1.5 to 2 h of image acquisition. Confidence was rated via Likert scale. Utilization was reported via indicating never, 1 to 2, 3 to 4, 5 to 6, or >6 times per month (recorded as 1-5, respectively). Image interpretation was assessed via a 6-question, multiple-choice video assessment. RESULTS: Nineteen of 99 potential residents (19%) completed a pre- and post-curriculum evaluation. Residents attended a median of 4 sessions. Confidence improved from 2.47 to 3.53 (P = .002). Utilization did not improve overall (2.11-2.42, P = .22), but utilization of left ventricular function assessment (1.53-2.00, P = .046) and pulmonary assessment (1.53-2.00, P = .039) increased. The percentage of residents that had ever changed their clinical management by POCUS increased from 47% to 84% after implementation of the curriculum. Cardiac, pulmonary/pleural, volume assessment, and abdominal free fluid exams were reported as the most clinically useful. CONCLUSION: Implementation of a longitudinal, academic half-day curriculum for POCUS resulted in improved confidence, increased POCUS utilization for the cardiac and pulmonary examination, and changes in clinical management based on POCUS.

Epcoritamab, a Novel, Subcutaneous CD3xCD20 Bispecific T-Cell-Engaging Antibody, in Relapsed or Refractory Large B-Cell Lymphoma: Dose Expansion in a Phase I/II Trial.

PURPOSE: Epcoritamab is a subcutaneously administered CD3xCD20 T-cell-engaging, bispecific antibody that activates T cells, directing them to kill malignant CD20+ B cells. Single-agent epcoritamab previously demonstrated potent antitumor activity in dose escalation across B-cell non-Hodgkin lymphoma subtypes. PATIENTS AND METHODS: In the dose-expansion cohort of a phase I/II study (ClinicalTrials.gov identifier: NCT03625037), adults with relapsed or refractory CD20+ large B-cell lymphoma and at least two prior therapy lines (including anti-CD20 therapies) received subcutaneous epcoritamab in 28-day cycles (once weekly step-up doses in weeks 1-3 of cycle 1, then full doses once weekly through cycle 3, once every 2 weeks in cycles 4-9, and once every 4 weeks in cycle 10 and thereafter) until disease progression or unacceptable toxicity. The primary end point was overall response rate by the independent review committee. RESULTS: As of January 31, 2022, 157 patients were treated (median age, 64 years [range, 20-83]; median of three [range, 2-11] prior therapy lines; primary refractory disease: 61.1%; prior chimeric antigen receptor (CAR) T-cell exposure: 38.9%). At a median follow-up of 10.7 months, the overall response rate was 63.1% (95% CI, 55.0 to 70.6) and the complete response rate was 38.9% (95% CI, 31.2 to 46.9). The median duration of response was 12.0 months (among complete responders: not reached). Overall and complete response rates were similar across key prespecified subgroups. The most common treatment-emergent adverse events were cytokine release syndrome (49.7%; grade 1 or 2: 47.1%; grade 3: 2.5%), pyrexia (23.6%), and fatigue (22.9%). Immune effector cell-associated neurotoxicity syndrome occurred in 6.4% of patients with one fatal event. CONCLUSION: Subcutaneous epcoritamab resulted in deep and durable responses and manageable safety in highly refractory patients with large B-cell lymphoma, including those with prior CAR T-cell exposure.

Systematic review of outcomes and patient heterogeneity in relapsed or refractory diffuse large B-cell lymphoma.

Aim: To evaluate trials of systemic therapies in transplant-ineligible or -experienced, relapsed/refractory diffuse large-B cell lymphoma and the impact of patient characteristics on overall response rate (ORR). Patients & methods: Systematically reviewed multiple databases through 22 July 2021. Analyzed variations in patient characteristics and their relationship with ORR across trials. Results: Among 17 included trials, key patient characteristics varied substantially: primary refractory (0-69%), refractory to last line of therapy (LOT) (12-100%), ≥2 prior LOTs (14-100%), ≥3 prior LOTs (0-64%), IPI ≥3 (23-73%), tumor stage III/IV (50-90%) and median age (56-74 years). ORRs varied substantially (25-83%), correlating with these characteristics. Conclusion: Differences in patient characteristics significantly contribute to the variability in ORR across these trials and should be considered when contextualizing efficacy data.

The Role of the Plantaris in Intramuscular Gastrocnemius Equinus Correction.

Equinus deformity is a common cause of foot and ankle pathology. The purpose of our study was to evaluate the role of the plantaris in equinus. Secondary aims were to describe the role of the plantaris in intramuscular gastrocnemius recession and to determine the prevalence of the plantaris in our patient population. We measured ankle dorsiflexion during the steps of a Baumann-type intramuscular gastrocnemius recession. Eighty-nine patients were enrolled in our study. Fourteen of 89 (15.7%) patients did not have a plantaris. A mean dorsiflexion of 9 (interquartile range 6-12)° was obtained after transection of the plantaris tendon and an additional mean 8 (interquartile range 5-10)° was obtained after recession of the gastrocnemius aponeurosis. There was a strong positive correlation (rs = 0.842) of dorsiflexion increase after plantaris transection and dorsiflexion increase after gastrocnemius recession (p < .00). Linear regression showed that for every one-degree of dorsiflexion increase with plantaris transection, there was a predicted dorsiflexion increase of 0.69° with gastrocnemius recession. These results indicate that the plantaris is a component of equinus deformity.

Anterior Ankle Incision Healing Complications With and Without Tourniquet Use: A Retrospective Comparative Cohort Study.

Anterior ankle incisions and tourniquet use in foot and ankle surgery have both been associated with increased incidence of incisional healing complications. Although a tourniquet is commonly used for procedures such as total ankle replacement and ankle arthrodesis that utilize an anterior ankle incision, it is possible to avoid tourniquet use while preserving adequate visualization with atraumatic layered dissection and closure, appropriate use of electrocautery, and ligation of vessels as needed. The primary aim of this study is to report rates of anterior ankle incisional healing complications both with and without tourniquet use. A retrospective chart review was performed on consecutive patients undergoing total ankle replacement or ankle arthrodesis through a multi-provider foot and ankle surgery practice between 2013 and 2018. A total of 121 patients, 58 (47.9%) in the tourniquet group and 63 (52.1%) in the no-tourniquet group, were included in this study with a median follow-up period of 36 (range 2-96) months. There was a higher rate of incisional healing complications for the tourniquet group (5.2%) compared to the no-tourniquet group (3.2%), however this did not reach statistical significance (p = .670). There was no significant difference in operative time between the tourniquet and no-tourniquet group (p = .405). The overall incisional healing complication rate was 4.1%. Although avoiding tourniquet use alone does not appear to significantly reduce anterior ankle incisional healing complications, the described technique has yielded an overall lower rate of incisional complications compared to those commonly reported in the literature.

Semimechanistic Physiologically-Based Pharmacokinetic/Pharmacodynamic Model Informing Epcoritamab Dose Selection for Patients With B-Cell Lymphomas.

Epcoritamab is a CD3xCD20 bispecific antibody (bsAb) that induces T-cell-mediated cytotoxicity against CD20-positive B cells. Target engagement and crosslinking of CD3 and CD20 (trimer formation) leads to activation and expansion of T cells and killing of malignant B cells. The primary objective of the dose-escalation part of the phase I/II trial of epcoritamab was to determine the maximum tolerated dose, recommended phase II dose (RP2D), or both. For bsAbs, high target saturation can negatively affect trimer formation. The unique properties and mechanisms of action of bsAbs require novel pharmacokinetic (PK) modeling methods to predict clinical activity and inform RP2D selection. Traditional PK/pharmacodynamic (PD) modeling approaches are inappropriate because they may not adequately predict exposure-response relationships. We developed a semimechanistic, physiologically-based PK/PD model to quantitatively describe biodistribution, trimer formation, and tumor response using preclinical, clinical PK, biomarker, tumor, and response data from the dose-escalation part of the phase I/II trial. Clinical trial simulations were performed to predict trimer formation and tumor response in patients with diffuse large B-cell lymphoma (DLBCL) or follicular lymphoma (FL). Model-predicted trimer formation plateaued at doses of 48 to 96 mg. Simulation results suggest that the 48-mg dose may achieve optimal response rates in DLBCL and FL. Exposure-safety analyses showed a flat relationship between epcoritamab exposure and risk of cytokine release syndrome in the dose range evaluated. This novel PK/PD modeling approach guided selection of 48 mg as the RP2D and provides a framework that may be applied to other CD3 bsAbs.

Intensivist -Driven Ventilator Management Shortens Duration of Mechanical Ventilation in Coronary Artery Bypass Graft Surgery Patients.

BACKGROUND: Prolonged mechanical ventilation in post Coronary Artery Bypass Graft Surgery (CABG) is associated with deleterious effects including, increased ICU and hospital length of stay (LOS), infectious complications, and mortality. Standardized ventilator weaning protocols and the utilization of critical care physicians in post CABG patient care vary substantially among institutions. The purpose of this study was to evaluate if intensivist consultation in conjunction with a multidisciplinary, standardized ventilator weaning protocol improves outcomes in CABG patients. MATERIALS AND METHODS: We performed a single-center, retrospective, before-after cohort analysis at Miami Valley Hospital in Dayton, OH, a 970-bed community hospital. Patients were divided into two arms: the before cohort or delayed-consult group (critical care consult after six hours on ventilator) and after cohort or immediate-consult group (immediate critical care consult). All patients were weaned from ventilator using a standardized weaning protocol. RESULTS: A total of 764 patients were enrolled, 411 in the delayed-consult group and 353 in the immediate-consult group. The immediate-consult group had less time on initial mechanical ventilation than the delayed-consult group (5.86 ± 4.75 h vs. 6.00 ± 6.64 h, P = 0.038). The small advantages to immediate critical care consultation for higher percent of early extubations, fewer re-intubations, shorter ICU LOS, and lower rate of ICU readmission were not statistically significant. The two groups had similar ventilator free days, prolonged mechanical ventilation, hospital LOS, and in-hospital mortality. CONCLUSION: Our study suggests that intensivist-driven ventilator management in conjunction with a multidisciplinary standardized weaning protocol shortens duration of mechanical ventilation in coronary artery bypass graft surgery patients.

Characteristics, Treatment, and Outcomes of Patients With Severe or Life-threatening COVID-19 at a Military Treatment Facility-A Descriptive Cohort Study.

INTRODUCTION: The treatment of severe and life-threatening COVID-19 is a rapidly evolving practice. The purpose of our study was to describe the characteristics and outcomes of patients with severe or life-threatening COVID-19 who present to a Military Treatment Facility (MTF) with an emphasis on addressing institutional adaptations to rapidly changing medical evidence. MATERIALS AND METHODS: A single-center retrospective study conducted on a prospectively maintained cohort. The MTF is a 52-bed hospital within an urban setting. Patients were included in the cohort if they had laboratory-confirmed severe or life-threatening COVID-19 with positive SARS-CoV-2 reverse transcription polymerase chain reaction. Severe disease was defined as dyspnea, respiratory frequency ≥30/min, blood oxygen saturation ≤93% on ambient air, partial pressure of arterial oxygen to fraction of inspired oxygen ratio <300, or lung infiltrates involving >50% of lung fields within 24-48 hours. Life-threatening COVID-19 was defined as respiratory failure, septic shock, or multiple organ dysfunction. The cohort included patients admitted from June 1 through November 13. Data were collected retrospectively via chart review by a resident physician. RESULTS: In total, our MTF saw 14 cases of severe or life-threatening COVID-19 from June 1 to November 13. Patients had a median age of 70.5 years, with 7% being active duty personnel, 21% dependents, and 71% retired military members. The median time to dexamethasone, remdesivir, and convalescent plasma administration was 4.7, 6.3, and 11.2 hours, respectively. The 28-day in-hospital mortality was 0%. CONCLUSIONS: Patients who present to an MTF with severe or life-threatening COVID-19 are largely retirees, with only a small fraction comprising active duty personnel. The institution of order sets and early consultation can help facilitate prompt patient care for COVID-19.

A retrospective cohort study assessing acute kidney injury and renal recovery among septic patients empirically treated with vancomycin piperacillin-tazobactam versus vancomycin cefepime.

Vancomycin plus piperacillin-tazobactam (VPT) is a commonly used antimicrobial regimen for septic patients. VPT is more nephrotoxic than other regimens such as vancomycin plus cefepime (VC) when given over several days. This risk of nephrotoxicity is less clear when VPT is given for initial empiric therapy in sepsis and de-escalated quickly based on evolving clinical information. The objective of this study was to assess nephrotoxicity among septic patients empirically treated with either VPT or VC at initial clinical presentation. We conducted a retrospective study of septic patients who received VPT or VC within 12 h of presentation to the emergency department. The primary outcomes were acute kidney injury (AKI) and renal recovery 72 h after presentation. For the total of 418 patients, 306 received VPT and 112 received VC. Rates of AKI at 72 h were 15.2% for VPT patients and 11.0% for VC patients [p = 0.44]. Among patients with AKI at presentation, 16.3% of VPT patients had AKI at 72 h compared to 8.9% of VC patients [p = 0.19]. Among those without AKI at presentation, 14.2% VPT patients and 16.7% VC patients had AKI at 72 h [p = 0.71]. Renal recovery rates for patients with AKI at presentation were 42.3% for VPT patients versus 40.3% for VC patients [p = 0.78]. In-hospital renal replacement therapy occurred in 6.2% VPT patients and 0.9% VC patients [p = 0.024]. Therefore, initial empiric therapy with VPT in sepsis may not confer increased risk of AKI when de-escalated appropriately.